Reagent and processes for targeting mutant epidermal growth factor receptors

Abstract

Vaccines comprising peptides from a fusion junction present in a mutant human EGF receptor and methods of using these vaccines in the inhibition of tumor formation and enhancement of tumor regression are provided. Cell lines which overexpress a Type III mutant EGF receptor and methods of producing these cell lines are also provided. In addition, antibodies raised against peptides expressed by these cell lines are provided. Further, antisense oligonucleotides targeted to a mutant EGF receptor which decreases expression of a mutant EGF receptor are disclosed.

What is claimed is:  
     
       1. A method of inhibiting formation or growth of tumors bearing a naturally occurring Type III mutant EGF receptor in a human subject comprising inducing a cytotoxic T-cell response against the tumor by administering to said subject a vaccine comprising a peptide having at least an amino acid sequence proximal to and including the amino acid at position  5  of the corresponding normal mature EGF receptor amino acid sequence for said subject followed by a glycine and an amino acid sequence distal to and including the amino acid at position  274  of the mature normal EGF receptor. 
     
     
       2. A method according to claim  1  wherein the vaccine comprises a peptide having the amino acid sequence SEQ ID NO: 1. 
     
     
       3. A method of inducing regression of an existing tumor bearing a naturally occurring Type III mutant EGF receptor in a human subject comprising inducing a cytotoxic T-cell response against the tumor by administering to said subject a vaccine comprising a peptide having at least an amino acid sequence proximal to and including the amino acid at position  5  of the corresponding normal mature EGF receptor sequence amino acid sequence for said subject followed by a glycine and an amino acid sequence distal to and including the amino acid at position  274  of the normal mature EGF receptor. 
     
     
       4. A method according to claim  3  wherein the vaccine comprises a peptide having the amino acid sequence SEQ ID NO: 1. 
     
     
       5. A method of inducing cytotoxic T-lymphocyte activity specifically directed against tumor cells expressing naturally occurring Type III mutant EGF receptor in a human subject comprising administering to said subject a vaccine comprising a peptide having at least an amino acid sequence proximal to and including the amino acid at position  5  of the corresponding normal mature EGF receptor amino acid sequence for said subject followed by a glycine and an amino acid sequence distal to and including the amino acid at position  274  of the mature normal EGF receptor. 
     
     
       6. A method according to claim  5  wherein the vaccine comprises a peptide having the amino acid sequence SEQ ID NO: 1. 
     
     
       7. A method of immunizing a human subject against tumors bearing type III mutant EGF receptors, comprising: 
       (a) providing a human subject at risk for developing a tumor comprising tumor cells expressing type III mutant EGF receptors;  
       (b) administering a vaccine to said subject comprising a peptide having at least an amino acid sequence proximal to and including the amino acid at position  5  of the corresponding normal mature human EGF receptor amino acid sequence followed by a glycine and an amino acid sequence distal to and including the amino acid at position  274  of the normal mature human EGF receptor such that a cytotoxic T-lymphocyte activity specifically directed against said tumor cells is generated; and  
       (c) determining that formation of said tumor is inhibited.  
     
     
       8. A method according to claim  7  wherein the vaccine comprises a peptide having the amino acid sequence SEQ ID NO:1. 
     
     
       9. A method of immunizing a human subject against tumors bearing type III mutant EGF receptors, comprising: 
       (a) providing a human subject having at least one said tumor comprising tumor cells expressing type III mutant EGF receptors;  
       (b) administering a vaccine to said subject comprising a peptide having at least an amino acid sequence proximal to and including the amino acid at position  5  of the corresponding normal mature human EGF receptor sequence amino acid sequence followed by a glycine and an amino acid sequence distal to and including the amino acid at position  274  of the normal mature human EGF receptor such that a cytotoxic T-lymphocyte activity specifically directed against said tumor cells is generated; and  
       (c) determining that growth of said tumor is inhibited.  
     
     
       10. A method according to claim  9  wherein the vaccine comprises a peptide having the amino acid sequence SEQ ID NO: 1. 
     
     
       11. A method of immunizing a human subject against tumors bearing type III mutant EGF receptors, comprising: 
       (a) providing a human subject having at least one said tumor comprising tumor cells expressing type III mutant EGF receptors;  
       (b) administering a vaccine to said subject comprising a peptide having at least an amino acid sequence proximal to and including the amino acid at position  5  of the corresponding normal mature human EGF receptor sequence amino acid sequence followed by a glycine and an amino acid sequence distal to and including the amino acid at position  274  of the normal mature human EGF receptor such that a cytotoxic T-lymphocyte activity specifically directed against said tumor cells is generated; and  
       (c) determining that said tumor has regressed.  
     
     
       12. A method according to claim  11  wherein the vaccine comprises a peptide having the amino acid sequence SEQ ID NO: 1.